Exercise does not induce browning of WAT at thermoneutrality and induces an oxidative, myogenic signature in BAT

Background and aimExercise training elicits diverse effects on brown (BAT) and white adipose tissue (WAT) physiology in rodents. However, these animals are typically housed below their thermoneutral zone (i.e. 28-32{degrees}C). In these conditions, BAT is chronically hyperactive and, unlike human residence, closer to thermoneutrality. Therefore, we set out to determine the effects of exercise training in obese animals at 28{degrees}C (i.e. thermoneutrality) on BAT and WAT in its basal (i.e. inactive) state.\n\nMethodsSprague-Dawley rats (n=12) were housed at thermoneutrality from 3 weeks of age and fed a high-fat diet (HFD). At 12 weeks of age half these animals were randomised to 4-weeks of exercise exercise training, i.e. swim-training (1 hour/day, 5 days per week). Metabolic assessment was undertaken during the final 48h and was followed by interscapular and perivascular BAT and inguinal (I)WAT sampling for the analysis of thermogenic genes and the proteome.\n\nResultsExercise attenuated weight gain but did not affect fat mass or general metabolic parameters (i.e. fasting insulin and glucose). Interestingly, although BAT mass was increased, there was no change in thermogenic gene expression. Differentially regulated proteins in BAT enriched gene ontology (GO) terms including 2-oxoglutarate metabolic process, cytochrome-c activity and mitochondrial respiratory chain complex IV. This was accompanied by an upregulation of multiple proteins and GO terms involved in skeletal muscle physiology suggesting an adipocyte to myocyte switch in BAT. UCP1 mRNA was undetectable in IWAT despite an increase in classical browning markers (i.e. PGC1a and ADRB3) with exercise. Enriched GO terms in IWAT included DNA binding and positive regulation of apoptosis. Impact analysis highlighted carbon metabolism and OXPHOS pathways were regulated by exercise in BAT whilst HIF-1 signalling and cytokine-cytokine receptor interaction were among those modified in IWAT.\n\nConclusionExercise training reduces weight gain in obese animals at thermoneutrality and is accompanied by an oxidative, myogenic signature in BAT, rather than induction of thermogenic genes. This may represent a new, UCP1-independent pathway through which BAT regulates body weight at thermoneutrality.